Amelioration of experimentally induced inflammatory arthritis by intra-articular injection of visnagin.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia, cartilage destruction and bone erosion. Visnagin (VIS) is a proven anti-inflammatory agent and in this study, we aimed to evaluate the anti-arthritic activity of VIS when administered via intra-articular (I.A.) route of administration. Materials and methods: RAW 264.7 â€‹cells were stimulated with lipopolysaccharide (LPS) (1 â€‹µg/mL) and treated with VIS at concentrations of 12.5 and 25 â€‹µM. Arthritis was induced in Sprague Dawley rats by administering Complete Freund's Adjuvant (CFA) (1 â€‹mg/mL) through (I.A.) route and treated with VIS via (I.A.) route at doses of 3 and 10 â€‹mg/kg twice a week for 3 weeks. Protective effects were assessed by arthritic score, behavioral studies for pain evaluation, radiological assessment, histopathological examination and molecular studies. Results: Our results indicated that VIS significantly reduced LPS induced inflammation in RAW 264.7 â€‹cells. While in arthritic rats, VIS reduced the disease scorings with improvement towards pain. Pathological examination demonstrated that VIS reduced knee joint inflammation and cartilage destruction. Radiographic analysis and molecular studies also supported the protective effects of VIS. Conclusion: The results of the study imply that VIS exerted potential anti-inflammatory and anti-arthritic activity in in vitro and in vivo models of RA.

Co-treatment of Nimbolide augmented the anti-arthritic effects of methotrexate while protecting against organ toxicities.

Prolonged exposure to the pharmacological doses of disease-modifying anti-rheumatic drugs (DMARDs) often results in major organ toxicities resulting in poor patient compliance. Methotrexate (MTX) is one of the commonly prescribed DMARDs for the treatment of arthritis, which results in vital organ dysfunction. To retain the anti-arthritic activity of MTX with the reduction in toxicities, combination therapies are warranted. Nimbolide (NMB) is a potent anticancer, anti-inflammatory and anti-fibrotic agent whose potential has been demonstrated in various pre-clinical models. Monoarthritis was developed with Complete Freund's Adjuvant in the knees of Wistar rats and treatment was given with either NMB (3 mg/kg/day) or MTX (2 mg/kg/week) alone or combination therapy (NMB + MTX). The anti-arthritic effects were evaluated by arthritic scoring, radiological imaging, synovial tissue proteins analysis, and histopathological staining. While hepato-renal toxicity was assessed in serum by evaluating the kidney and liver functional parameters, in tissues by oxidative-nitrosative stress markers, and pro-inflammatory cytokines levels. Histopathological analysis was performed to study the extent of tissue damage. Molecular studies like immunoblotting and immunohistochemistry were performed to understand the effect of combination therapy. We thereby report that monotherapy with either NMB or MTX exhibited significant anti-arthritic effects, while combination therapy resulted in augmented anti-arthritic effects with significant reduction in hepato-renal toxicity produced by MTX probably through anti-inflammatory and anti-oxidant effects. Therefore, our proposed combination of NMB and MTX may serve as a potential strategy for the effective management of arthritis.